DESCRIPTION (from the application): The long range goal of this program project is to understand the basic molecular mechanisms involved in human cellular senescence. The specific aims are to: 1) Bring together six individual laboratories using disparate model systems of cellular senescence: normal human fibroblasts, adrenocortical cells and melanocytes, various immortal human cell lines and animal models; to work together on similar goals, using common techniques and approaches to answer questions regarding the molecular and cellular mechanisms involved in senescence and immortalization. These studies will examine the changes in gene expression that occur in cells as they age in vitro and in vivo, and will establish the differences and similarities in the pathways that lead to inhibition of cell proliferation. Recognizing that aging is a multi-faceted process, the individual projects will explore various mechanisms of age related changes in gene expression, including DNA methylation, chromatic structure, senescence specific transactivating factors and RNA binding proteins and the relevance of in vitro to in vivo aging. 2) Provide core facilities that are requisite for all the projects and thereby consolidate resources that will benefit the research at a much lower cost. The aims of a program project will thereby be met, encouraging successful interactions and enhancing the utilization of common resources. 3) Provide a formal mechanism to promote research interactions via joint planning meetings.